Original Research Early Signs of Inflammation With Mild Oxidative Stress in Mixed Martial Arts Athletes After Simulated Combat Jos ´ e Alberto Fernandes Gomes-Santos, 1 Rafael Herlich Lambertucci, 2 Cristina Vasconcelos Vardaris, 1 Maria Elizabeth Pereira Passos, 1 Edenilson Pinto Silva-Junior, 1 Elaine Hatanaka, 1 Renata Gorja ˜ o, 1 Steven Roy McAnulty, 3 T´ acito Pessoa Souza-Junior, 3,4 and Marcelo Paes de Barros 1 1 Program in Health Sciences, Institute of Physical Activity and Sports Science (ICAFE), Cruzeiro do Sul University, Sa ˜o Paulo, SP, Brazil; 2 Department of Human Movement Sciences, Institute for Health and Society, Federal University of Sa ˜o Paulo (UNIFESP), Santos, Sa ˜o Paulo, Brazil; 3 Department of Health & Exercise Science, Appalachian State University, Boone, North Carolina; and 4 Department of Physical Education, Federal University of Parana (UFPR), Curitiba, Puerto Rico, Brazil Abstract Gomes-Santos, JAF, Lambertucci, RH, Vardaris, CV, Passos, MEP, Silva-Junior, EP, Hatanaka, E, Gorja ˜ o, R, McAnulty, SR, Souza- Junior, TP, and Barros, MP. Early signs of inflammation with mild oxidative stress in Mixed Martial Arts athletes after simulated combat. J Strength Cond Res XX(X): 000–000, 2019—Combat sports involve a combination of strenuous physical activity, usually at the anaerobic threshold, followed by intermittent low-intensity recovery periods for energy re-establishment. Oxidative stress and inflammation are inevitable exercise-related processes that could drastically affect athletic performance and practitioners’ health, unless efficiently con- trolled during and after physical activities. This study aims to measure oxidative stress and inflammation biomarkers in the plasma of 12 top ranked professional Mixed Martial Arts (MMAs) athletes before and after simulated combats under official rules (pre-post study). Our results show that the athletes exhibited mild oxidative imbalances in plasma, evidenced by significant (p , 0.01) higher contents of both reduced (+7.3%) and oxidized glutathione (+28%), uric acid (+21%), and “free” iron (+21%) after combat, whereas variation tendencies (0.05 , p , 0.01) were observed in the antioxidant capacity in plasma ( 240%), and SOD (227%) or GPX (+20%) antioxidant activities in erythrocytes. However, a clear pro-inflammatory state was detected by increases in circulating cytokines IL-6 (+6,020%), IL-1b (+4,357%), and tumor necrosis factor alpha (+63%), and by an abrupt drop of the anti-inflammatory cytokine IL-10 (298%). A significant correlation was observed between pre-post variations of IL-6 and GSH/GSSG ratio in plasma (p , 0.0001), which reinforces the integration between oxidative stress and inflammation during MMA combats. Considering metabolic and mechanical stresses (imposed by combat techniques, e.g., punches and joint locks), this study indicates pre-existing inflammation, although minor oxidative stress, in MMA professionals after combat. Key Words: antioxidant, exercise, combat sport, cytokine, free radicals, iron Introduction The Mixed Martial Arts (MMAs) practice was first mentioned in 649 BC as part of the ancient competition Pankration, which was created to introduce different combat skills to Greek soldiers (27). Nowadays, MMA competitions have been attracting thousands of fans worldwide, especially after 2009, when the implementation of restricted rules ensured safety in this sport. After upgraded regula- tion, a decreasing number of severe injuries and concussions legiti- mated MMA as a combat sport by improving the integrity and health of MMA athletes (45). Despite its increasing popularity, MMA coaches, physiologists, physicians, nutritionists, and athletes still lack solid scientific information about physiological, metabolic, and molecular processes responsible for obtaining maximum per- formance with lower risks of injuries and illness from recurrent cycles of intense training/low-quality recovery periods (31). The current state-of-art of MMA physiology/biochemistry relates more to its constituent combat sports (jiujitsu, wrestling, Muay Thai, etc.), than to the combination of them into a single sport category. It is well-established that general exercise increases the pro- duction of reactive oxygen species/reactive nitrogen species (ROS/ RNS) in muscle tissues, vascular endothelium, and human plasma (38). The oxidative condition imposed by different forms of ex- ercise apparently affects iron homeostasis as well, both in sed- entary and trained individuals (24). Many cellular sources contribute to the enhanced ROS/RNS production during exercise such as the mitochondrial respiratory chain, cytosolic O 2 -de- pendent xanthine oxidase (XO), and reduced nicotinamide ade- nine dinucleotide-phosphate (NADPH) oxidase in vascular and myocyte membranes (13). Different types and intensities of ex- ercise may switch the contributions of ROS/RNS sources in contracting skeletal muscles, epithelial cells, and other organs, culminating in redox imbalances also in plasma. When in excess, ROS/RNS mediate oxidative modifications in proteins, lipids, and nucleic acids that could cause cellular dysfunctions and ill- ness, if not properly counteracted by local and systemic antioxi- dant defenses (46). The frontline of cellular antioxidant defenses is provided by highly-efficient enzymes, such as superoxide dis- mutase (SOD), catalase (CAT), and glutathione peroxidase Address correspondence to Dr. Marcelo Paes de Barros, marcelo.barros@ cruzeirodosul.edu.br. Journal of Strength and Conditioning Research 00(00)/1–7 ª 2019 National Strength and Conditioning Association 1 Copyright © 2019 National Strength and Conditioning Association. Unauthorized reproduction of this article is prohibited.